Among the stimuli to which cells are exposed in vivo, it has been shown that tensile deformations induce specific cellular responses in musculoskeletal, cardiovascular, and stromal tissues. However, the early response of cells to sustained substrate-based stretch has remained elusive because of the short timescale at which it occurs. To measure the tensile mechanical properties of adherent cells immediately after the application of substrate deformations, we have developed a dynamic traction force microscopy method that enables subsecond temporal resolution imaging of transient subcellular events.
View Article and Find Full Text PDFAlthough the molecular mechanisms behind tendon disease remain obscure, aberrant stromal matrix turnover and tissue hypervascularity are known hallmarks of advanced tendinopathy. We harness a tendon explant model to unwind complex cross-talk between the stromal and vascular tissue compartments. We identify the hypervascular tendon niche as a state-switch that gates degenerative matrix remodeling within the tissue stroma.
View Article and Find Full Text PDFUnderstanding cell-material interactions requires accurate characterization of the substrate mechanics, which are generally measured by indentation-type atomic force microscopy. To facilitate cell-substrate interaction, model extracellular matrix coatings are used although their tensile mechanical properties are generally unknown. In this study, beyond standard compressive stiffness estimation, we performed a novel tensile mechanical characterization of collagen- and fibronectin-micropatterned polyacrylamide hydrogels.
View Article and Find Full Text PDFOsteosarcoma is the most frequent primary tumor of bone and is characterized by its high tendency to metastasize in lungs. Although treatment in cases of early diagnosis results in a 5-yr survival rate of nearly 60%, the prognosis for patients with secondary lesions at diagnosis is poor, and their 5-yr survival rate remains below 30%. In the present work, we have used a number of analytical methods to investigate the impact of increased metastatic potential on the biophysical properties and force generation of osteosarcoma cells.
View Article and Find Full Text PDFThe surgical standard of care for lumbar discectomy leaves the annulus fibrosus (AF) defect unrepaired, despite considerable risk for a recurrent herniation. Identification of a viable defect repair strategy has until now been elusive. The scope of this ex vivo biomechanical study was to evaluate crosslinking hydrogels as potentially promising AF defect sealants, and provide a baseline for their use in combination with collagen scaffolds that restore disc volume.
View Article and Find Full Text PDFBackground: The suture-tendon interface is often the weakest link in tendon-to-tendon or tendon-to-bone repair. Genipin is an exogenous collagen crosslink agent derived from the gardenia fruit that can enhance suture force to failure of the tendon-suture interface. Viable methods for intraoperative clinical delivery of genipin could be of clinical utility, but to our knowledge have not yet been extensively studied.
View Article and Find Full Text PDFThe accurate determination of cellular forces using Traction Force Microscopy at increasingly small focal attachments to the extracellular environment presents an important yet substantial technical challenge. In these measurements, uncertainty regarding accuracy is prominent since experimental calibration frameworks at this size scale are fraught with errors - denying a gold standard against which accuracy of TFM methods can be judged. Therefore, we have developed a simulation platform for generating synthetic traction images that can be used as a benchmark to quantify the influence of critical experimental parameters and the associated errors.
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